Commentary - The FHA domain mediates phosphoprotein interactions

The forkhead-associated (FHA) domain is a phosphopeptide-binding domain fir st identified in a group of forkhead transcription factors but is present i n a wide variety of proteins from both prokaryotes and eukaryotes, In yeast and human, many proteins containing an FHA. domain are found in the nucleu s and involved in DNA repair, cell cycle arrest, or pre-mRNA processing. In plants, the FHA domain is part of a protein that is localized to the plasm a membrane and participates in the regulation of receptor-like protein kina se signaling pathways. Recent studies show that a functional FI-IA domain c onsists of 120-140 amino acid residues, which is significantly larger than the sequence moth first described. Although FHA domains do not exhibit exte nsive sequence similarity, they share similar secondary and tertiary struct ures, featuring a sandwich of two anti-parallel P-sheets. One intriguing fi nding is that FHA domains may bind phosphothreonine, phosphoserine and some times phosphotyrosine, distinguishing them from other well-studied phosphop rotein-binding domains. The diversity of proteins containing FHA. domains a nd potential differences in binding specificities suggest the FHA domain is involved in coordinating diverse cellular processes.